title: Analysis of CD40 expression in breast cancer and its relation to clinicopathological characteristics.
abstract: Breast cancer is currently the most common cancer in women worldwide. For this reason, new biomarkers for better predicting response to treatment are needed. CD40, described as expressed in haematological and epithelial tumors, is linked to apoptosis and offers promise as a new predictive/ prognostic marker. We evaluated CD40 expression in formalin-fixed, paraffin-embedded samples from 181 breast carcinomas using immunohistochemical staining with CD40 antibody. Samples were divided according to hormone (oestrogen receptor /ER/, progesterone receptor /PR/) and her-2/neu status into groups: 1.Luminal A (ER+PR+her-2/neu-), 2. Luminal B (ER+PR+her-2/neu+), 3.Triple-negative (ER-PR-her-2/neu-) and 4. Her-2/neu (ER-PR-her-2/neu+). The results of CD40 staining were correlated with clinicopathological data. CD40 was found to be expressed in membrane, cytoplasm and nucleus. Normal ducts expressed cytoplasmic CD40 in 30% of cases, in breast tumor ducts in 53% of cases. CD40 was evaluated as an independent marker and significant positive correlation was found with Bcl-2 (p =0.002), early stage (p =0.016) and preoperative chemotherapy (p =0.043). There was higher overall survival for patients with cytoplasmic CD40 expression (0.05). Differences in expression of cytoplasmic CD40 between groups with different hormonal and her-2/neu status were statistically highly significant (p=0.00003). In groups with different hormonal status, a positive statistical correlation was found for the luminal A group with relapse (p=0.024) and stage (p=0.006). No correlation was found with age, disease onset, family history of cancer/ breast cancer, patient history, hormonal replacement therapy, menopausal status at onset of disease, adjuvant chemotherapeutic treatment or disease free survival. Nuclear expression of CD40 was found to be unrelated to any clinicopathological data. However, there was higher ratio of positive cases in cancer cases (83%) than in normal tissue (30%). In conclusion, cytoplasmic expression of CD40 is related to factors connected to better prognosis and suggest that CD40 may have potential as a new prognostic factor in breast cancer.
authors.affiliation: Laboratory of Molecular Pathology, Institute of Pathology, Faculty of Medicine and Dentistry, Palacky University and University Hospital, Hnevotinska 3, 775 15 Olomouc, Czech Republic. slobodova.zuzana@seznam.cz
authors.forename: Z
authors.initials: Z
authors.lastname: Slobodova
authors.forename: J
authors.initials: J
authors.lastname: Ehrmann
authors.forename: V
authors.initials: V
authors.lastname: Krejci
authors.forename: J
authors.initials: J
authors.lastname: Zapletalova
authors.forename: B
authors.initials: B
authors.lastname: Melichar
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000737:chemistry* / Q000401:mortality / Q000473:pathology*; D019013:CD40 Antigens / Q000032:analysis* / Q000502:physiology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis
chemical_list: D019013:CD40 Antigens; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C508053:ERBB2 protein, human